Colon cancer is a major medical problem in the United States today. It is the second leading cause of death with 52,000 deaths per year reported. The distribution of colon cancer, particularly its infrequency in Japan, its increase among Japanese immigrants to Hawaii, and the high incidence of this disease in North Americans and Northwest Europeans indicates that an environmental factor is of etiological significance in the development of this disease. Furthermore, evaluation of the dietary habits of populations with different risks suggest that dietary factors, particularly high intake of dietary fat and beef, have a strong association with large bowel cancer. Populations in high risk areas consume diets with large portions of fat and beef whereas people in low risk areas consume diets which are low in these components, but rish in vegetable protein. The roles played by sterols, bile acids and their metabolites as either carcinogens, co-carcinogens, or inhibitors in large bowel cancer are the objectives of the proposed research. In order to define more precisely the importance of plant sterols, neural sterols, bile acids and their metabolites, we will study the effect of induced changes of the colonic concentrations of these compounds on cancer development in rats given carcinogens. In addition, we will examine the possible retarding effect of plant sterols in large bowel cancer and the role of sulfation on colon cancer. Metabolites of neutral sterols and bile acid, such as cholesterol epoxide and iso-bile acids, will be studied to determine their possible role in colon carcinogenesis. From these studies, we hope to be able to identify patients at high risk of developing cancer and develop means of decreasing the risk.